Developing innovative chemistry methodology to efficiently synthesise novel heterocycles as fragments.

Prof Paul Wyatt. Head of the Drug Discovery Unit, and Director of the Wellcome Centre for Anti-Infectives Research, University of Dundee is seeking a highly motivated and enthusiastic synthetic organic or medicinal chemist to carry out a PhD focused on developing innovative chemistry methodology to efficiently synthesise novel heterocycles as fragments. Fragments are low molecular weight and low complexity organic molecules suitable for initiating drug discovery projects.

The research will be within the DDU (www.drugdiscovery.dundee.ac.uk/), which is part of the Wellcome Centre for Anti-Infectives Research (WCAIR). The DDU is working to discover and facilitate the development of new drugs for major diseases, e.g. malaria, TB, cancer, neurodegeneration. WCAIR is housed in a state-of-the-art building and has cutting-edge equipment and automation for synthetic chemistry and drug discovery. The successful applicant will join a dynamic and multidisciplinary group that covers all aspects of drug discovery up to candidate selection.

As a long term goal, the DDU is exploring replacing high throughput biochemical screening for drug targets, with high throughput fragment screening (e.g. high throughput X-ray crystallography) followed by enhanced computational approaches to optimise fragment hits into leads. To achieve this we must develop high quality fragment libraries that cover a very broad range of chemical space. Fortunately, there are thousands of medicinal chemistry relevant heterocycles unreported in the literature that would enrich fragment screening sets and be useful as building blocks for medicinal chemistry campaigns.

The project will focus on developing new array chemistry methodology to efficiently synthesise these multiple novel heterocycles. The approaches will involve a broad range of synthetic chemistry reactions, using flow chemistry, plate-based chemistry, catch and release methodology, solid supported reagents, and scavengers. Dundee has a range of flow and array equipment for synthesis and purification to facilitate this project.

Within the project you will significantly develop your knowledge and experience of:
• Theory and practice of synthetic and medicinal chemistry, and fragment based drug discovery
• Using computational methods for synthesis route evaluation to design effective and efficient synthetic chemistry strategies across multiple compounds
• A broad range of synthetic transformations
• Developing new synthetic methodology, including plate based chemistry and in flow

This will be gained working in conjunction with the multi-disciplinary teams of the DDU and computational chemistry groups. In addition, experience of supervision could be gained by supervising summer and project students.

The post is available from now.

Generation of Polar Semi-Saturated Bicyclic Pyrazoles for Fragment-Based Drug-Discovery Campaigns, Luise, N.; Wyatt, P.G. Chemistry - A European Journal, 2018, 24(41), 10443-10451

Fragment library design, synthesis and expansion: nurturing a synthesis and training platform, Ray, P.C.; Kiczun, M.; Huggett, M.; Lim, A.; Prati, F.; Gilbert, I.H.; Wyatt, P.G. Drug Discovery Today, 2017, 22(1), 43-56

Skills and Knowledge

Required
• At least a BSc or equivalent in chemistry or medicinal chemistry
• Demonstrable expertise in organic chemistry theory and principles
• A willingness to work flexibly to meet milestones
• Good time management and organisational skills
• Strong interpersonal, communication and presentation skills

Desirable
• General IT skills

A few facts about The School of Life Sciences at Dundee:

• The School of Life Sciences has over 900 research and support staff from 59 countries and external funding in excess of £40 million per year
• Dundee has twice been named ‘the best place to work in Europe’ in a poll of scientists conducted by The Scientist magazine
• The University of Dundee achieved the highest aggregate rating in Biology among all UK Universities in the 2014 Research Excellence Framework (REF) assessment.
• The 2017 ‘The State of Innovation’ report by Clarivate Analytics ranked Dundee as the most influential scientific research institution in pharmaceuticals for the period 2006-16.

Dundee, set on the east coast of Scotland, lies in an area of outstanding natural beauty, including large sandy beaches and challenging hills.

How to apply:

To apply on-line please visit: http://www.lifesci.dundee.ac.uk/apply-now

The University of Dundee is a diverse community and is committed to equality of opportunity for all by providing a supportive, flexible and inclusive working environment. We have family friendly policies (including flexible working and childcare vouchers), staff groups for LGBT and BME; and prayer room facilities.

The University of Dundee has received the Athena SWAN Bronze Award (http://www.dundee.ac.uk/about/athenaswan/) which recognises the promotion of gender equality and has made further commitment to advancing inclusive culture which supports and encourages all under-represented groups.

The University of Dundee is a Scottish Registered Charity, No. SC015096.